Cold insoluble globulin (CIg), also known as fibronectin, is a major glycoprotein of vertebrate blood and organ stroma. Fibroblasts and endothelial cells in cell culture synthesize CIg and may act as the sources of circulating CIg in vivo. CIg apparently interacts with platelets, fibrinogen and coagulation factor XIII in vitro; however, its physiologic significance and function have not been established. Many of the existing methods to isolate CIg for study were inadequate. An efficient technique has been examined to purify CIg in large quantities and to render it free of contaminating coagulation proteins and inhibitors. This technique will also provide a means to analyze the interactions between purified coagulation proteins and CIg.